Peripheral T cell Lymphoma, NOS Flashcards
What is the definition of
peripheral T cell lymphoma, NOS ?
- heterogeneous category of nodal and extranodal mature T cell lymphomas
- do not fit into any specific entity
- typically presents in adults and has an aggressive clinical course
What are the epidemiology and etiology
for PTCL, NOS?
- account for ~30% of PTCLs in western countries
- very rare in children, usually adults
- male:female ratio is 2:1
- EBV infection is reported in a small number of cases
- usually EBV is found in the background cells
What is the localization of
PTCL, NOS ?
- most patients have peripheral lymph node involvement, but any site can be affected
- advanced stage disease is common
- bone marrow, liver, spleen, extranodal tissue
- usually sin and GI tract
- other less frequently involved sites include CNS and lung
- peripheral blood sometimes involved but leukemic presentation is uncommon
- bone marrow, liver, spleen, extranodal tissue
What are the clinical features ?
- often patients present with enlarged lymph nodes
- most have advanced stage disease with B symptoms
- rarely paraneoplastic syndromes can be seen:
- eosinophilia
- pruritis
- hemophagocytic syndrome
What are the microscopic findings
of PTCL, NOS ?
- paracortical or diffuse infiltrates with effacement of normal lymph node architecture
- broad cytological spectrum
- most cases: medium to large lymphocytes with irregular, pleomorphic , hyperchromatic or vesicular nuclei
- prominent nucleoli and many mitotic figures
- clear cells with RS cell morphology can be seen
- rare cases with predominantly small lymphoid cells can be seen
- Note:
- features of AITL should not be seen
What is the inflammatory background
like in PTCL, NOS?
- mixed inflammatory background is often present
- small lymphocytes, plasma cells, eosinophils
- large B cells (may be clonal irrespective of EBV infection)
- clusters of epithelioid histiocytes
What is the pattern of splenic involvement ?
- pattern of involvement is variable
- solitary or multiple fleshy nodules
- diffuse white pulp involvement with colonization of the PALS
- or diffuse red pulp involvement
What is a common variant of
PTLC, NOS ?
- Lymphoepithelioid lymphoma
- also known as Lenner Lymphoma
- shows interfollicular growth
- Cytology
- predominantly small cells with slight nuclear irregularities
- numerous and sometimes confluent epithelioid histiocytes
- occasional, atypical proliferating blasts
- admixed inflammatory cells with scattered R-S like cells that are usually EBV positive
- IMP: HEV are not prominent
What is the immunophenotype
usually of the lymphoepithelioid variant ?
- most cases are CD8+
- cytotoxic profile
Note: this variant may have a somewhat better prognosis
What should you watch out for
in general with T cell neoplasms and PTCL, NOS ?
- sometimes they can only involve the paracortical region and surround reactive germinal centers
- may mimic benign paracortical hyperplasia
What is the pattern of growth of
primary EBV-positive nodal T-cell
and NK-cell lymphomas ?
- usually infiltrate in a monomorphic pattern
- no angiodestruction and necrosis
- unlike Extranodal NK-T cell lymphoma
- for now they are considered a variant of PTCL, NOS
What is the immunophenotype
of PTCL, NOS ?
- frequently down regulate CD5 and CD7
- usually CD4 positive
- but double positive, or negative as well as CD8 have been seen
- CD56 positive
- cytotoxic granules positive
What helps differentiate PTCL, NOS from
gamma-delta T cell lymphomas and extranodal
NK-T cell lymphomas ?
- expression of T cell receptor beta
What immunophenotype can rarely
be expresed in PTCL, NOS?
- CD15 and CD30 positivity
Note: these cases may show features overlapping with those of ALK-negative ALCL
Expression of what immunohistochemical
marker demonstrates a poor prognosis ?
- CD15 expression shows a poor prognosis
Expression of what two other markers may
have prognostic significance ?
- TBX21 (also known as T-BET)
- GATA3
These may be important for subclassification
What other markers can be seen
in PTCL, NOS?
- expression of a single TFH marker can be seen once in a while
- CD52 (40%)
- CD30 >25% expression in half the cases
- cut off value for treatment is elusive
- CD30+ does not seem to respond to treatment as well as ALCL
Aberrant expression of what markers
can occasionally be seen ?
- CD20 and CD79a
- CD15
What is the proliferation index usually ?
- high, >70%
What is the postulated normal counterpart
of PTCL, NOS ?
- activated mature T cells
- usually the CD4+ memory type of the adaptive immune system
What is the genetic profile of PTCL, NOS?
- TR genes are clonally rearranged in most
- highly aberrant neoplasms with complex karyotypes with recurrent chromosomal gains and losses
- aberrations differ from other T cell lymphomas like AITL and ALCL
- gene expression profiling has identified subgroups
- TBX21 (T-BET)
- GATA3
- no specific gene mutations have been attributed yet to PTCL,NOS
What types of molecules are TBX21 and GATA3 ?
- transcription factors that are master regulators of gene expression profiles in T helper cells
- TBX21 may promote TH1 cells
- GATA3 may promote TH2 cells
- still has to be proven
What is the differential diagnosis
of PTCL, NOS ?
- ALK(-) ALCL
- especially since CD30 is highly expressed in a subset of PTCL, NOS, but not strong and uniform as in ALCL
- also ALCL will have more pronounced cytotoxic marker positivity and EMA
- IMP:
- ALCL carries genomic abberations in DUSP22 and TP53 that have not been shown in PTCL, NOS
What are the prognostic and predictive
markers seen in PTCL, NOS ?
- these are highly aggressive lymphomas with poor response to therapy
- frequent relapses
- IPI score only prognostic thing right now
What morphologic findings have been
proposed as prognostic factors ?
- involvement of the bone marrow
- Ki67 proliferation index >70%
these are negative prognostic factors
What findings are proposed as poor
prognosis in PTCL, NOS ?
- EBV positivity
- NF-KappaB pathway dysregulation
- a high proliferation signature by gene expression
- GATA3 expression
- >70% transformed cells
- cytotoxi profile
- CD30 in most or all cells
